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ACS Nano. 2019 Jan 22;13(1):260-273. doi: 10.1021/acsnano.8b05602. Epub 2019 Jan 9.

Nanolongan with Multiple On-Demand Conversions for Ferroptosis-Apoptosis Combined Anticancer Therapy.

Bao W1,2,3, Liu X1,2,3, Lv Y2, Lu GH2, Li F2, Zhang F2, Liu B1, Li D1, Wei W2, Li Y1.

Author information

1
Beijing Advanced Innovation Center for Food Nutrition and Human Health, Key Laboratory of Functional Dairy, College of Food Science and Nutritional Engineering , China Agricultural University , 100083 Beijing , China.
2
State Key Laboratory of Biochemical Engineering , Institute of Process Engineering, Chinese Academy of Sciences , 100190 Beijing , China.
3
College of Life Science and Technology , Beijing University of Chemical Technology , 100029 Beijing , China.

Abstract

As a type of programmed cell death, ferroptosis is distinct from apoptosis. The combination of the two thus provides a promising modality with which to significantly improve anticancer treatment efficacy. To fully utilize this combination, we herein designed a nanolongan delivery system, which possessed a typical structure of one core (up-conversion nanoparticles, UCNP) in one gel particle (Fe3+ cross-linked oxidized starch) with multiple on-demand conversions. The charge conversion of the nanolongan surface in a slightly acidic microenvironment enhanced circulation time for utilizing the enhanced permeability and retention effect, enabled efficient uptake by tumor cells, and induced subsequently lysosomal escape. As the core component, the UCNP with light conversion from near-infrared light to ultraviolet light circumvented the impediment of limited penetration depth and enabled the reduction of Fe3+ to Fe2+. Accordingly, gel networks of nanolongan could be deconstructed due to this valence conversion, leading to the rapid release of Fe2+ and doxorubicin (Dox). In this case, the Fenton reaction between Fe2+ and intracellular H2O2 generated potent reactive oxygen species for ferroptosis, while the co-released Dox penetrated into nucleus and induced apoptosis in a synergistic way. As a result, superior anticancer therapeutic effects were achieved with little systemic toxicity, indicating that our nanolongan could serve as a safe and high-performance platform for ferroptosis-apoptosis combined anticancer therapy.

KEYWORDS:

NIR-responsive; anticancer; combined therapy; ferroptosis; multiple on-demand responsive; nanolongan

PMID:
30616348
DOI:
10.1021/acsnano.8b05602

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